Acetyl chloride → N-(6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-1,3-dimethyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)acetamide

HRID 13822Notes

Reaction equation

HRID 13822 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[N:7][C:8]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=3[Cl:26])=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=3)[CH:10]=2)[N:5]([CH3:27])[C:4](=[O:28])[C:3]=1[CH3:29].[H-].[Na+].[C:32](Cl)(=[O:34])[CH3:33].CCN(CC)CC>C1COCC1.CN(C=O)C>[Cl:18][C:15]1[CH:14]=[CH:13][C:12]([C:9]2[CH:10]=[C:11]3[C:6](=[N:7][C:8]=2[C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=2[Cl:26])[N:5]([CH3:27])[C:4](=[O:28])[C:3]([CH3:29])=[C:2]3[NH:1][C:32](=[O:34])[CH3:33])=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 6367Acetyl chloride2×HCID 8471Triethylamine2×HCID 24758Sodium hydrideHCID 11247790HCID 11247790, compound

Product 1

HCID 11167681N-(6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-1,3-dimethyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the product of EXAMPLE 40 (72 mg) in THF (3 mL) and DMF (0.2 mL) was added NaH (10 mg, 60% dispersion in mineral oil) followed by acetyl chloride (30 μL). After stirring 30 minutes at room temperature NEt3 (45 μL) was added. After an additional hour of reaction time TLC indicated incomplete reaction. Acetyl chloride (15 μL) and NEt3 (45 μL) was added to the reaction, however this generated the imide (N-acetyl-N-(7-(2,4-dichlorophenyl)-6-(4-chlorophenyl)-1,2-dihydro-1,3 dimethyl-2-oxo-1,8-naphthyridinyl)acetamide). The reaction was quenched with methanol and NaHCO3, diluted with EtOAc and washed with 2 M aqueous HCl followed by 1 M aqueous NaOH solution. The solution was concentrated and the residue in 8 mL of 2:1 THF:methanol was treated with CS2O3 (80 mg). TLC indicated conversion of the imide to the amide after about 10 minutes at room temperature. The reaction was concentrated, dissolved in EtOAc and washed with brine. The concentrated solution was then purified by flash chromatography (silica gel) gradient eluted with 0-90% EtOAc in hexane affording the title compound. HPLC/MS: 486.0 (M+1), 488.0 (M+3); Rt=4.24 min.

Workup

  1. additionwas added
  2. customAfter an additional hour of reaction time TLC
  3. customreaction
  4. customThe reaction was quenched with methanol and NaHCO3
  5. additiondiluted with EtOAc
  6. washwashed with 2 M aqueous HCl
  7. concentrationThe solution was concentrated
  8. additionthe residue in 8 mL of 2:1 THF:methanol was treated with CS2O3 (80 mg)
  9. customafter about 10 minutes
  10. customat room temperature
  11. concentrationThe reaction was concentrated
  12. dissolutiondissolved in EtOAc
  13. washwashed with brine
  14. customThe concentrated solution was then purified by flash chromatography (silica gel) gradient
  15. washeluted with 0-90% EtOAc in hexane affording the title compound

Sources & evidence

ORD record
ord-2c0cb3aa0f004c7f976eda6717209b4f
Source dataset
uspto-grants-2010_06
Patent number
US07728141B2

Reaction notes

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